1 Results version history

2 Description of results

Outcomes:

Ancestry data:

Association analysis

Multi-trait association analysis

2.1 Significannt thresholds

2.1.1 Bonferroni threshold

0.05 / 229384
[1] 2.179751e-07

3 Results

3.1 Interaction with SmokCigNow

3.1.1 Manhattan plots

3.1.2 Chr 11, PARVA gene

3.1.2.1 Fine-mapping

Table of top SNP and other SNPs from the same ancestry segment (chr11acs76906):

snp zscore pval chr pos acs num_snps size trait
rs933920 2.928 0.003413 11 12481110 chr11acs76906 21 36273 FEV1pp_utah
rs4756884 -2.557 0.01055 11 12474098 chr11acs76906 21 36273 FEV1pp_utah
rs4756866 -2.369 0.01781 11 12448846 chr11acs76906 21 36273 FEV1pp_utah
rs10831815 2.076 0.03792 11 12446924 chr11acs76906 21 36273 FEV1pp_utah
rs10741590 2.056 0.03976 11 12463318 chr11acs76906 21 36273 FEV1pp_utah
rs1344615 -1.901 0.05725 11 12454046 chr11acs76906 21 36273 FEV1pp_utah
rs11022358 1.647 0.09951 11 12470449 chr11acs76906 21 36273 FEV1pp_utah
rs10831827 -1.603 0.1089 11 12483197 chr11acs76906 21 36273 FEV1pp_utah
rs1365403 1.571 0.1161 11 12476231 chr11acs76906 21 36273 FEV1pp_utah
rs1346220 1.543 0.1229 11 12480087 chr11acs76906 21 36273 FEV1pp_utah

3.2 Interaction with SmokCigNow0_15

3.2.1 Manhattan plots

3.2.2 Chr 11

3.2.2.1 Fine-mapping

3.2.2.1.1 COPD and Obstructive Sleep Apnea

COPD; Mesh term

All MeSH Categories
  Diseases Category
  Respiratory Tract Diseases
    Lung Diseases
      Lung Diseases, Obstructive
        Pulmonary Disease, Chronic Obstructive

Obstructive Sleep Apnea; Mesh Term

Categorization 1:

All MeSH Categories
  Diseases Category
    Respiratory Tract Diseases
      Respiration Disorders
        Apnea
          Sleep Apnea Syndromes
            Sleep Apnea, Obstructive

Categorization 2:

All MeSH Categories
  Diseases Category
    Nervous System Diseases
      Sleep Wake Disorders
        Dyssomnias
          Sleep Disorders, Intrinsic
            Sleep Apnea Syndromes
              Sleep Apnea, Obstructive

3.2.3 Chr 10

3.2.3.1 Fine-mapping

  • BICC1 gene: This gene encodes an RNA-binding protein that is active in regulating gene expression by modulating protein translation during embryonic development. Mouse studies identified the corresponding protein to be under strict control during cell differentiation and to be a maternally provided gene product.

3.2.4 Chr 2

3.2.4.1 Fine-mapping

4 QQ plots

4.1 Interaction with SmokCigNow

4.2 Interaction with SmokCigNow0_15

5 Quality control on multi-trait analysis

5.1 Interaction with SmokCigNow

5.2 Interaction with SmokCigNow0_15

6 Models formulas

trait ver formula
FEV1pp_utah 9 imp_FEV1pp_utah ~ Age_Enroll + gender + Duration_Smoking + log_CigPerDaySmokAvg + SmokCigarNow + SmokCigNow + SmokCigNow0_15 + acs_global2 + (0 + dummy(SmokCigNow0_15Rev)|rsid1) + (0 + dummy(SmokCigNowRev)|rsid2) + (1|ccenter)
FEV1_utah 9 imp_FEV1_utah ~ Age_Enroll + Age_Enroll2 + gender + Height_CM + Duration_Smoking + log_CigPerDaySmokAvg + SmokCigarNow + SmokCigNow + SmokCigNow0_15 + acs_global2 + (0 + dummy(SmokCigNow0_15Rev)|rsid1) + (0 + dummy(SmokCigNowRev)|rsid2) + (1|ccenter)
FVCpp_utah 9 imp_FVCpp_utah ~ Age_Enroll + gender + Duration_Smoking + log_CigPerDaySmokAvg + SmokCigarNow + SmokCigNow + SmokCigNow0_15 + acs_global2 + (0 + dummy(SmokCigNow0_15Rev)|rsid1) + (0 + dummy(SmokCigNowRev)|rsid2) + (1|ccenter)
FVC_utah 9 imp_FVC_utah ~ Age_Enroll + Age_Enroll2 + gender + Height_CM + Duration_Smoking + log_CigPerDaySmokAvg + SmokCigarNow + SmokCigNow + SmokCigNow0_15 + acs_global2 + (0 + dummy(SmokCigNow0_15Rev)|rsid1) + (0 + dummy(SmokCigNowRev)|rsid2) + (1|ccenter)
FEV1_FVC_utah 9 imp_FEV1_FVC_utah ~ Age_Enroll + Age_Enroll2 + gender + Duration_Smoking + log_CigPerDaySmokAvg + SmokCigNow + SmokCigNow0_15 + acs_global2 + (0 + dummy(SmokCigNow0_15Rev)|rsid1) + (0 + dummy(SmokCigNowRev)|rsid2) + (1|ccenter)
log_pctEmph_Slicer 9 imp_log_pctEmph_Slicer ~ Age_Enroll + gender + Duration_Smoking + log_CigPerDaySmokAvg + SmokCigarNow + SmokCigNow + SmokCigNow0_15 + acs_global2 + (0 + dummy(SmokCigNow0_15Rev)|rsid1) + (0 + dummy(SmokCigNowRev)|rsid2) + (1|ccenter) + (1|scanner_gr)
TLCpp_race_adjusted 9 imp_TLCpp_race_adjusted ~ Age_Enroll + gender + Duration_Smoking + log_CigPerDaySmokAvg + SmokCigarNow + SmokCigNow + SmokCigNow0_15 + acs_global2 + (0 + dummy(SmokCigNow0_15Rev)|rsid1) + (0 + dummy(SmokCigNowRev)|rsid2) + (1|ccenter)

7 R code for the Omnibus test

Test Statistics Distribution Reference
Omnibus \(z^T \Sigma^{-1} z\) \(\chi^2(p)\) (Aschard et al., in preparation)
sumZ \((1^T z)^2 / 1^T \Sigma^{-1} 1\) \(\chi^2(1)\) (Province et al, 2013) 
  jtab <- switch(method,
    "omnibus" = {
      P1 <- tcrossprod(Z, Sigma_inv)
      P2 <- P1 * Z # element-wise multiplication
      z2score <- rowSums(P2)
      
      data_frame(z2score = z2score) %>%
        mutate(pval = pchisq(z2score, df = ncol(Z), lower = FALSE))
    },
    "metacp" = {
      P1 <- tcrossprod(Z, Sigma_inv)
      
      z2score <- (rowSums(P1))^2 / sum(Sigma_inv)
      
      data_frame(z2score = z2score) %>%
        mutate(pval = pchisq(z2score, df = 1, lower = FALSE))
    },
    "sum2" = {
      z2score <- (rowSums(Z))^2 / sum(Sigma)
      
      data_frame(z2score = z2score) %>%
        mutate(pval = pchisq(z2score, df = 1, lower = FALSE))
    },    
    stop("switch"))